{"id":632,"date":"2017-04-25T04:18:15","date_gmt":"2017-04-25T09:18:15","guid":{"rendered":"http:\/\/www.bocsci.com\/blog\/?p=632"},"modified":"2017-04-25T04:18:15","modified_gmt":"2017-04-25T09:18:15","slug":"functions-and-role-of-the-fatty-acid-synthase-pathway-and-its-end-products","status":"publish","type":"post","link":"https:\/\/www.bocsci.com\/blog\/functions-and-role-of-the-fatty-acid-synthase-pathway-and-its-end-products\/","title":{"rendered":"Functions and Role of the Fatty acid synthase Pathway and its End Products"},"content":{"rendered":"

In highly lipogenic tissues such as the liver, adipose and lactating breast, the Fatty acid synthase<\/a>\u00a0(FAS)\u00a0catalyzed fatty acid synthesis pathway has three main functions: 1) the conversion of excess\u00a0caloric intake into triacylglycerols for storage, 2) synthesis of fat from carbohydrate and protein\u00a0when dietary sources of fat are lacking, and 3) synthesis of fat in the breast during lactation.<\/p>\n

Palmitate, the major endproduct of the FAS pathway, is primarily esterified and stored as\u00a0a triacylglycerol in liver and adipose tissue. When needed, triacylglycerols are exported to other sites where they are used for energy in metabolic functions such as cell repair and cell cycling. In the lactating breast, fatty acids are produced to provide energy for the baby, but shorter chain\u00a0fatty acids such as myristate are produced instead for ease of digestion. Aside from being utilized as a source of energy, palmitate and other minor fatty acids\u00a0have been shown to be involved in cell signaling. For example, acute exposure of human\u00a0pancreatic islets to palmitate causes an up-regulation of tyrosine phosphorylation of insulin\u00a0receptors. As well, protein palmitoylation has been implicated in the modification of\u00a0several different proteins, particularly in G-protein coupled receptors. These G-proteins are\u00a0crucial in cellular signaling processes and palmitoylation is thought to modify G-protein\u00a0phosphorylation and membrane translocation, In addition, many palmitoylated proteins are\u00a0found to be concentrated in lipid rafts. In special lipid rafts called caveolae, palmitate is also\u00a0present and is thought to contribute to processes such as ras <\/i><\/em>and raf <\/i><\/em>signaling as well as caveolae\u00a0stability and cholesterol transport.
\nDespite the important role palmitate plays in the cellular activities, it is not an essential\u00a0fatty acid. A person consuming an adequately balanced diet will obtain sufficient amounts of fat,\u00a0and therefore undergo minimal endogenous fatty acid synthesis. Even in tissues with high\u00a0cellular turnover, circulating fatty acids are preferentially used as structural lipids over\u00a0endogenously produced ones. Because of the low activity, there are few diseases that\u00a0directly involve the fatty acid synthesis pathway, although variations of FAS<\/a> activity still may\u00a0have an influence on diseases such as obesity and diabetes. Nonetheless, fatty acid synthesis is\u00a0crucial for development. In mice, FAS homozygous knockouts are non-viable, with most of the\u00a0embryos dying before implantation. As well, most heterozygous FAS knockout mice die at\u00a0various stages of embryonic development.\u00a0Surviving heterozygous mice possess 50% and\u00a035% lower FAS mRNA and activity compared to wild types, suggesting that the lack of FAS
\ngene has significant teratogenic consequences. Additionally, conditional knockout FASKOL\u00a0(FAS knockout in liver) mice develop fatty livers and liver disease when consuming fat free diets. In these mice, fatty acids are mobilized from the adipose tissue to the liver. However, due\u00a0to the liver\u2019s inability to synthesize new fatty acids, the incoming fatty acids are not oxidized and\u00a0build up. This suggests that FAS, is necessary to maintain normal health and that a basal level of\u00a0de novo fatty acid synthesis is required.<\/p>\n

Production of endogenous fatty acids begins with the substrate acetyl-CoA that is\u00a0available in the cytosol. The other critical starting substrate is malonyl-CoA, and its production\u00a0from acetyl-CoA is the initial rate-limiting step in fatty acid synthesis. In the presence of\u00a0bicarbonate and ATP, acetyl-CoA is converted to malonyl-CoA by acetyl-CoA carboxylase. In a\u00a0two-step reaction, the enzyme transfers a carboxyl group from the bicarbonate to acetyl-CoA,\u00a0forming malonyl-CoA. Both of these substrates are then used in fatty acid chain elongation, a\u00a0multi-step process that is completely catalyzed by FAS. <\/b><\/strong>Initially, acetyl-CoA, acting as\u00a0a primer molecule, combines with the cysteine SH group on the FAS molecule, catalyzed by\u00a0acetyl transacylase. Malonyl-CoA is then transferred to the adjacent SH\u00a0group (which is located on ACP), catalyzed by malonyl transacylase, forming an acyl(acetyl)-malonyl enzyme. Next, 3-ketoacyl synthase liberates CO2\u00a0from the acyl chain,\u00a0decarboxylating the chain and driving the reaction further downstream. The chain is then\u00a0reduced (3-ketoacyl reductase), dehydrated (dehydratase) and reduced again (enoyl\u00a0reductase)\u00a0to form a saturated four-carbon acyl enzyme. The chain then enters this sequence\u00a0of reactions six more times, with a new malonyl-CoA being incorporated into the chain each\u00a0sequence until a saturated 16-carbon palmitate is formed. The fatty acid is then cleaved\u00a0from FAS by thioesterase, and is activated by the addition of a CoA residue before it is utilized\u00a0for metabolic functions. Although the major endproduct is palmitate, in some tissues there are\u00a0separate thioesterase enzymes that specifically cleave fatty acids of length 8, 10, 12, or 18 carbon\u00a0atoms, resulting in a variety of fatty acids being produced by FAS.<\/p>\n

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Reference:<\/h4>\n

Lau, Dominic Sze Yan.\u00a0Fatty Acid Synthase and Cancer: Expression and Interaction with Conjugated Linoleic Acid<\/i><\/em>. ProQuest, 2007.<\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

In highly lipogenic tissues such as the liver, adipose and lactating breast, the Fatty acid synthase\u00a0(FAS)\u00a0catalyzed fatty acid synthesis pathway has three main functions: 1) the conversion of excess\u00a0caloric intake […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[147],"tags":[421],"_links":{"self":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/632"}],"collection":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/comments?post=632"}],"version-history":[{"count":1,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/632\/revisions"}],"predecessor-version":[{"id":633,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/632\/revisions\/633"}],"wp:attachment":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/media?parent=632"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/categories?post=632"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/tags?post=632"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}